Recent studies suggest that diastolic left ventricular filling dysfunction may be a sensitive indicator of myocardial ischemia. At present, however, neither the normal spatial and temporal pattern of regional diastolic left ventricular dynamics, nor the changes in regional diastolic wall dynamics resulting from ischemia have been precisely defined. The overall objective of the experiments proposed in this application is to define the nature of regional diastolic wall motion and wall thinning in the normal myocardium and to assess the alterations produced by ischemia. Specifically, we want to address the following questions: (1) Does the pattern of diastolic wall motion and wall thinning vary systematically at different levels of the left ventricle from base to apex? Does it vary systematically in different segments at a given level of the ventricle? (2) What is the relationship between regional myocardial blood flow by layer and regional diastolic wall dynamics during graded reduction in perfusion? Does regional diastolic wall dysfunction occur prior to systolic abnormalities as blood flow decreases? (3) What are the effects of permanent coronary occlusion on diastolic wall dynamics in the infarcted, adjacent and opposite non-ischemic regions? What is the relationship between regional diastolic dysfunction and global diastolic left ventricular performance? Investigations addressing these questions will be performed in canine models. We will employ two-dimensional echocardiography and construct regional diastolic filling curves and wall thinning curves. We will measure regional myocardial perfusion with radiolabelled microspheres, determine risk area by autoradiography and map infarct zone by pathological examination. Knowlege gained from these studies will contribute to the understanding of regional diastolic filling in the normal and ischemic myocardium. Our long range goal is to extend these studies in humans to interpret the role of regional diastolic left ventricular function in determining the clinical manifestations of ischemic heart disease.